Q96RI0 (PAR4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proteinase-activated receptor 4
Short name=PAR-4

Alternative name(s):
Coagulation factor II receptor-like 3
Thrombin receptor-like 3

Gene names

Name:	F2RL3
Synonyms:	PAR4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	385 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation. Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Widely expressed, with highest levels in lung, pancreas, thyroid, testis and small intestine. Not expressed in brain, kidney, spinal cord and peripheral blood leukocytes. Also detected in platelets.
Post-translational modification	A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Blood coagulation Hemostasis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phospholipase C-activating G-protein coupled receptor signaling pathway Traceable author statement Ref.3. Source: ProtInc platelet activation Traceable author statement. Source: Reactome platelet dense granule organization Inferred by curator PubMed 18480058. Source: BHF-UCL positive regulation of release of sequestered calcium ion into cytosol Inferred from direct assay PubMed 18480058. Source: BHF-UCL
Cellular_component	extracellular region Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement Ref.3. Source: ProtInc
Molecular_function	thrombin receptor activity Traceable author statement PubMed 10500152. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Propeptide

18 – 47

30

Removed for receptor activation By similarity

PRO_0000012762

Chain

48 – 385

338

Proteinase-activated receptor 4

PRO_0000012763

Regions

Topological domain

48 – 82

35

Extracellular Potential

Transmembrane

83 – 103

21

Helical; Name=1; Potential

Topological domain

104 – 108

5

Cytoplasmic Potential

Transmembrane

109 – 129

21

Helical; Name=2; Potential

Topological domain

130 – 151

22

Extracellular Potential

Transmembrane

152 – 172

21

Helical; Name=3; Potential

Topological domain

173 – 192

20

Cytoplasmic Potential

Transmembrane

193 – 213

21

Helical; Name=4; Potential

Topological domain

214 – 247

34

Extracellular Potential

Transmembrane

248 – 268

21

Helical; Name=5; Potential

Topological domain

269 – 283

15

Cytoplasmic Potential

Transmembrane

284 – 304

21

Helical; Name=6; Potential

Topological domain

305 – 319

15

Extracellular Potential

Transmembrane

320 – 343

24

Helical; Name=7; Potential

Topological domain

344 – 385

42

Cytoplasmic Potential

Compositional bias

301 – 305

5

Poly-Leu

Sites

Site

47 – 48

2

Cleavage; by thrombin or trypsin By similarity

Amino acid modifications

Glycosylation

56

1

N-linked (GlcNAc...) Potential

Disulfide bond

149 ↔ 228

By similarity

Natural variations

Natural variant

120

1

A → T. Ref.1 Ref.2 Ref.3
Corresponds to variant rs773902 [ dbSNP | Ensembl ].

VAR_028300

Natural variant

215

1

R → Q.
Corresponds to variant rs2230799 [ dbSNP | Ensembl ].

VAR_028301

Natural variant

296

1

F → V. Ref.5
Corresponds to variant rs2227346 [ dbSNP | Ensembl ].

VAR_012852

Natural variant

310

1

P → L. Ref.5
Corresponds to variant rs2227376 [ dbSNP | Ensembl ].

VAR_012853

Experimental info

Mutagenesis

47

1

R → A: No proteolytic cleavage (by thrombin or trypsin). Ref.3

Mutagenesis

68

1

R → A: No effect on receptor activation. Ref.3

Secondary structure

1

.

.

.

385

Helix Strand Turn

Details...

Beta strand

44 – 46

3

Sequences

	Sequence		Length	Mass (Da)
	Q96RI0 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: FACE32F10D5C561E	FASTA	385	41,133
	10 20 30 40 50 60 MWGRLLLWPL VLGFSLSGGT QTPSVYDESG STGGGDDSTP SILPAPRGYP GQVCANDSDT 70 80 90 100 110 120 LELPDSSRAL LLGWVPTRLV PALYGLVLVV GLPANGLALW VLATQAPRLP STMLLMNLAA 130 140 150 160 170 180 ADLLLALALP PRIAYHLRGQ RWPFGEAACR LATAALYGHM YGSVLLLAAV SLDRYLALVH 190 200 210 220 230 240 PLRARALRGR RLALGLCMAA WLMAAALALP LTLQRQTFRL ARSDRVLCHD ALPLDAQASH 250 260 270 280 290 300 WQPAFTCLAL LGCFLPLLAM LLCYGATLHT LAASGRRYGH ALRLTAVVLA SAVAFFVPSN 310 320 330 340 350 360 LLLLLHYSDP SPSAWGNLYG AYVPSLALST LNSCVDPFIY YYVSAEFRDK VRAGLFQRSP 370 380 GDTVASKASA EGGSRGMGTH SSLLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene and locus structure and chromosomal localization of the protease-activated receptor gene family." Kahn M.L., Hammes S.R., Botka C., Coughlin S.R. J. Biol. Chem. 273:23290-23296(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-120.
[2]	"A dual thrombin receptor system for platelet activation." Kahn M.L., Zheng Y.-W., Huang W., Bigornia V., Zeng D., Moff S., Farese R.V. Jr., Tam C., Coughlin S.R. Nature 394:690-694(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-120.
[3]	"Cloning and characterization of human protease-activated receptor 4." Xu W.-F., Andersen H., Whitmore T.E., Presnell S.R., Yee D.P., Ching A., Gilbert T., Davie E.W., Foster D.C. Proc. Natl. Acad. Sci. U.S.A. 95:6642-6646(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF ARG-47 AND ARG-68, VARIANT THR-120. Tissue: Lymphoma.
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." King M.M., Aronstam R.S., Sharma S.V. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[5]	SeattleSNPs variation discovery resource Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-296 AND LEU-310.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin." Kahn M.L., Nakanishi-Matsui M., Shapiro M.J., Ishihara H., Coughlin S.R. J. Clin. Invest. 103:879-887(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF080214 mRNA. Translation: AAC28860.1.
AF055917 mRNA. Translation: AAC25699.1.
AY431102 mRNA. Translation: AAR08487.1.
AF384819 Genomic DNA. Translation: AAK61908.1.
BC074782 mRNA. Translation: AAH74782.2.

IPI

IPI00022557.

RefSeq

NP_003941.2. NM_003950.2.

UniGene

Hs.137574.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZPK	X-ray	1.80	P/Q	46-53	[»]
3QDZ	X-ray	2.80	E/F	39-47	[»]

ProteinModelPortal

Q96RI0.

SMR

Q96RI0. Positions 51-357.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000248076.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

Q96RI0.

Polymorphism databases

DMDM

116242700.

Proteomic databases

PaxDb

Q96RI0.

PRIDE

Q96RI0.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000248076; ENSP00000248076; ENSG00000127533.

GeneID

9002.

KEGG

hsa:9002.

UCSC

uc002nfa.3. human.

Organism-specific databases

CTD

9002.

GeneCards

GC19P017001.

HGNC

HGNC:3540. F2RL3.

MIM

602779. gene.

neXtProt

NX_Q96RI0.

PharmGKB

PA27949.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG148814.

HOGENOM

HOG000116291.

HOVERGEN

HBG096365.

InParanoid

Q96RI0.

KO

K04236.

OMA

YYVSAEF.

OrthoDB

EOG4KD6MW.

PhylomeDB

Q96RI0.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

Bgee

Q96RI0.

CleanEx

HS_F2RL3.

Genevestigator

Q96RI0.

GermOnline

ENSG00000127533. Homo sapiens.

Family and domain databases

InterPro

IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003944. Prot_act_rcpt_4.
IPR003912. Protea_act_rcpt.
[Graphical view]

Pfam

PF00001. 7tm_1. 1 hit.
[Graphical view]

PRINTS

PR00237. GPCRRHODOPSN.
PR01428. PROTEASEAR.
PR01430. PROTEASEAR4.

PROSITE

PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q96RI0.

ChEMBL

CHEMBL4691.

EvolutionaryTrace

Q96RI0.

GenomeRNAi

9002.

NextBio

33761.

PMAP-CutDB

Q96RI0.

SOURCE

Search...

Entry information

Entry name

PAR4_HUMAN

Accession

Primary (citable) accession number: Q96RI0
Secondary accession number(s): O76067, Q6DK42

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 115 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.